MicroRNAs or miRNAs are short sequences of RNA (20-24 nucleotide molecules) that function by altering the stability or translational efficiency of targeted mRNAs. There has been a significant amount of recent research into miRNAs that has attempted to determine their full scope, mechanism of action and disease association. Products associated with the understanding and clinical application of miRNAs will likely play a strong part in the future of medical care. Given the importance of miRs during different biological processes, tools for repression of miR function may be useful for research and have therapeutic potential. MicroRNAs are thought to regulate tumor progression and invasion via direct interaction with target genes within cells.
Bone grafts are the second most transplanted tissue/material in the United States. Autografts and allografts are the current standard strategies for surgical intervention and subsequent bone repair, but each possesses limitations, such as donor-site morbidity with the use of autograft and the risk of disease transmission with the use of allograft. In order to overcome these inherent limitations, synthetic bone-graft substitutes based on tissue engineering strategies represent an alternative approach. Recombinant human BMP-2 (rhBMP-2), delivered using an absorbable collagen sponge, has been approved by the Food and Drug Administration (FDA) for inducing spinal fusion, fracture healing, and filling bony defects following tumor resection. In dentistry, rhBMP-2 has been used in alveolar ridge and sinus augmentation. Recombinant human BMP-7 (rhBMP-7) is authorized by the FDA as a humanitarian device for use as an autograft alternative for recalcitrant long bone nonunions. There has been a tremendous increase in rhBMP usage as a bone graft substitute in the past few years. In 2009, close to 1.5 billion dollars were spent on bone graft substitutes, half of which was attributed to rhBMPs. However, the outcome of rhBMP treatment may be far from satisfactory. Serious adverse events can occur after the use of rhBMP-2 in oral and maxillofacial procedures. The same study also revealed rising complication rates following BMP-2 administration both in FDA cleared and off-label indications. The high cost associated with rhBMP therapy and the reported adverse events following its usage in supra physiological doses strongly underscore the need to develop an alternative approach that is safer, more cost-effective, and highly efficient for bone regeneration.
One in approximately 2,500 live births in the United States has congenital anomalies collectively called craniosynostosis (premature suture fusion). Children suffering from craniosynostosis may develop severe secondary neurological disorders associated with increased intracranial pressure. The current standard of therapy is resection of fused sutures to release abnormal intracranial pressure and to correct the resulting progressive esthetic deformity. However, this surgical procedure is associated with high morbidity and higher rates of re-synostosis due to an unexpected extremely high osteogenic potential of calvarial bone in craniosynostosis patients. The role of cytokines, especially transforming growth factor (TGF)-β family members and fibroblast growth factors (FGF), participates extensively in suture biology and etiopathogenesis of craniosynostosis. Specifically, FGF-2, TGF-β1, 2, and bone morphometric protein (BMP)-2 have been demonstrated to play critical roles both in pathological and physiological suture osseous fusion by up-regulating the proliferation and differentiation of osteoblasts and their progenitor cells. Therefore, in order to prevent premature sutural osseous fusion there is a critical need to develop novel strategies to inhibit the excessive signaling that are generated by these osteogenic cytokines.